Genetic Variant SEMA5B:p.Met1023Val (chr3-122911515-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001031702.4(SEMA5B):c.3067A>G(p.Met1023Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEMA5B
NM_001031702.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578

Publications

0 publications found

Variant links:

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SEMA5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031582475).

BP6

Variant 3-122911515-T-C is Benign according to our data. Variant chr3-122911515-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2245642.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031702.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA5B	NM_001031702.4	MANE Select	c.3067A>G	p.Met1023Val	missense	Exon 21 of 23	NP_001026872.2	Q9P283-1
SEMA5B	NM_001256347.1		c.3229A>G	p.Met1077Val	missense	Exon 21 of 23	NP_001243276.1	Q9P283-4
SEMA5B	NM_001437563.1		c.3139A>G	p.Met1047Val	missense	Exon 21 of 23	NP_001424492.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA5B	ENST00000357599.8	TSL:1 MANE Select	c.3067A>G	p.Met1023Val	missense	Exon 21 of 23	ENSP00000350215.3	Q9P283-1
SEMA5B	ENST00000451055.6	TSL:2	c.3229A>G	p.Met1077Val	missense	Exon 21 of 23	ENSP00000389588.2	Q9P283-4
SEMA5B	ENST00000616742.4	TSL:5	c.3067A>G	p.Met1023Val	missense	Exon 21 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458152

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25830

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111060

Other (OTH)

AF:

0.0000166

AC:

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.7

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.021

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.73

M_CAP

Benign

0.0022

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

PhyloP100

0.58

PrimateAI

Benign

0.26

PROVEAN

Benign

0.27

REVEL

Benign

0.025

Sift

Benign

0.63

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.037

MutPred

0.43

Gain of glycosylation at S1022 (P = 0.0444)

MVP

0.38

MPC

0.27

ClinPred

0.041

GERP RS

-2.2

Varity_R

0.042

gMVP

0.20

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over